DESCRIPTION (Applicant's abstract): A wealth of data, including a recent linkage study, suggest that abnormalities in smooth pursuit eye movements mark the schizophrenia phenotype. Deficits in vigilance, working memory and other neurocognitive functions are frequently observed in relatives of patients with schizophrenia and are considered putative phenotypic markers. In spite of these rich data, several issues remain unclear. What is the precise neurophysiologic mechanism underlying the pursuit abnormality in schizophrenia spectrum? Are various putative liability markers correlated? Are some of the cognitive measures marking a different dimension of the phenotype (or a different phenotype)? With these questions in mind, the application broadly aims to: i) apply refined methods of evaluating smooth pursuit eye movement function to studies in relatives of patients with schizophrenia in order to understand the neurobiology of genetic vulnerability to schizophrenia; ii) to demonstrate that the refined measures of smooth pursuit identify relatives at risk (i.e., relatives with schizophrenia spectrum personalities, SSP) with high accuracy as suggested by our preliminary data; and iii) to determine the relationship among various phenotypic markers and whether they make independent contributions in identifying a phenotype. We plan to recruit four groups of subjects (1) first degree biological relatives of schizophrenic patients with (n=30) and (2) without SSP symptoms (n=30), and (3) community subjects with no known family history of psychosis with (n=30) and (4) without SSP symptoms (n=6O). We will administer a battery of eye movement and neurocognitive tests in these groups of subjects. We have a specific hypothesis regarding the nature of smooth pursuit abnormality in schizotypy. This hypothesis will be assessed using ocular motor and other cognitive (e.g., working memory) tasks. Other neurocognitive measures will be compared in these four groups. And we will explore the ability of eye tracking measures alone, cognitive measures alone and the measures in combination in accurately predicting relative status.